Novel pyridinylpyrimidine derivatives, method for production thereof and a plant disease protectant containing them as the active ingredient

ABSTRACT

A novel pyridinylpyrimidine derivative of the formula below, a method for preparation thereof and a plant disease protectant containing it, ##STR1## which is effective as a plant disease protectant.

This invention relates to a novel pyridinylpyrimidine derivative, amethod for preparation thereof and a plant disease protectant containingit as an active ingredient.

The pyridinylpyrimidine derivatives such as4-methyl-2-(2-pyridinyl)pyrimidine (J. Org. Chem. 32, 1591, (1967)) andN,N-dimethyl-2-(6-methyl-2-pyridylpyrimidine-4-yl-thio)-ethyl amine(Aust. J. Chem., 35 1203 (1982)) are known.

However, it is not known that the pyridinylpyrimidine derivatives havefungicidal effect at all.

An object of the present invention is to provide a compound havingpreventive and curative controlling effects against many plant diseases.

The present inventors have found that pyridinylpyrimidine derivativeshaving the formula (I) mentioned below or a salt thereof (hereinafterreferred simply to as the present compound) have excellent fungicidalactivity: ##STR2## wherein R₁ may be the same or different and is loweralkyl such as C₁ -C₄ alkyl, lower alkoxy such as C₁ -C₄ alkoxy, lowerhaloalkyl whose alkyl is such as C₁ -C₄ alkyl, or halogen (fluorine,chlorine, bromine or iodine); n is 0, 1, 2, 3, 4 or 5; R₂ and R₃, whichmay be the same or different, each represent hydrogen or lower alkylsuch as C₁ -C₄ alkyl; R₄ is hydrogen or lower alkyl such as C₁ -C₃alkyl; R₅ is hydrogen, lower alkyl such as C₁ -C₃ alkyl or halogen(fluorine, chlorine, bromine or iodine), or R₄ and R₅ together representa polymethylene group of the formula: --CH₂ --_(m) in which m is 3 or 4;and R₆ is hydrogen, lower alkyl such as C₁ -C₃ alkyl, lower alkoxy suchas C₁ -C₃ alkoxy or lower alkylthio whose alkyl is such as C₁ -C₃ alkyl.

Preferably, R₁ may be the same or different and is lower alkyl such asC₁ -C₃ alkyl, lower alkoxy such as C₁ -C₃ alkoxy, lower haloalkyl whosealkyl is such as C₁ -C₃ alkyl, or halogen (fluorine, chlorine, bromineor iodine); n is 0, 1, 2 or 3; R₂ is hydrogen or methyl; R₃ is hydrogenor lower alkyl such as C₁ -C₄ alkyl; R₄ is hydrogen, methyl or ethyl; R₅is hydrogen, methyl, ethyl or halogen (fluorine, chlorine, bromine oriodine); and R₆ is hydrogen, methyl, ethyl, methoxy, ethoxy ormethylthio.

More preferably, R₁ may be the same or different and is selected frommethyl, ethyl, methoxy, C₁ or C₂ haloalkyl or halogen (fluorine orchlorine); n is 0, 1, 2 or 3; R₂ and R₃, which may be the same ordifferent, each represent hydrogen or methyl; R₄ is methyl; R₅ ishydrogen or methyl; and R₆ is hydrogen, methyl or methoxy.

Most preferably, R₁ may be the same or different and is methyl,trifluoromethyl, fluorine or chlorine, n is 0, 1 or 2; R₂ is hydrogen ormethyl; R₃ is hydrogen; R₄ is methyl; R₅ is hydrogen or methyl; and R₆is hydrogen or methyl.

Plant disease that are controlled by the present compound include thefollowings;

Rice: Pyricularia oryzae, Cochliobolus miyabeanus and Rhizoctoniasolani;

Barley and wheat: Erysiphe graminis f. sp. hordei, E. graminis f. sp.tritici, Pyrenophora graminea, Puccinia striiformis, P. graminis, P.recondita, P. hordei, Pseudocercosphorella herpotrichoides,Rhynchosporium secalis, Septoria tritici and Leptosphaeria nodorum;

Citrus: Diaporthe citri and Elsinoe fawcetti;

Apple: Podosphaera leucotricha, Alternaria mali and Venturia inaequalis;

Pear: Venturia mashicola and Alternaria kikuchina;

Peach: Sclerotinia cinerea;

Grape: Elsinoe ampelina, Glomerella cingulata and Uncinula necator;

Melon crops: Colletotrichum lagenarium and Sphaerotheca fuliginea;

Tomato: Alternaria solani and Phytophthora infestans;

Eggplant: Phomopsis vexans;

Rape: Alternaria japonica and Cercosporella brassicae;

Welsh onion: Puccinia allii;

Soybean: Cercospora kikuchii and Elsinoe glycines;

Kidney bean: Collectotrichum lindemuthianum;

Peanut: Mycosphaerella personatum and Cercospora arachidicola;

Pea: Erysiphe pisi;

Potato: Alternaria solani;

Sugar beet: Cercospora beticola;

Rose: Diplocarpon rosae and Sphaerotheca pannosa;

Crop plants: Botrytis cinerea and Sclerotinia sclerotiorum.

Diseases more controllable among the above are

Rice: Pyricularia oryzae, Rhizoctonia solani,

Barley and wheat: Septoria tritici, Pseudocercosporella herpotrichoides,and most controllable is Pyricularia oryzae against rice andPseudocercosporella herpotrichoides, Septoria tritici against barley andwheat.

The pyridinylpyrimidine derivative (I) is typically prepared by themethods as shown below:

Procedure (a):

A pyridinylpyrimidine derivative of the formula: ##STR3## wherein R₁,R₂, R₃, R₄, R₅ and n are the same as defined above and R₆ ' is hydrogen,is obtained by allowing a picoline amidine derivative of the formula:##STR4## wherein R₁, R₂, R₃ and n are the same as defined above, or asalt thereof to react, in the presence of a base, with β-oxoacetalderivative of the formula: ##STR5## wherein R₄ and R₅ are the same asdefined above and R₇ is lower alkyl such as C₁ -C₄ alkyl.

Examples of the salt of picoline amidine derivative are hydrochloride,hydrobromide, acetate and formate. Examples of such base are alkalimetal alkoxide such as sodium methoxide and sodium ethoxide and organicbase such as triethylamine and N,N-diethylaniline. Sodium methoxide orsodium ethoxide is preferable.

The reaction is usually carried out in the presence of an inert solventsuch as lower alcohol (e.g. methanol and ethanol), cyclic ether (e.g.dioxane and tetrahydrofuran), pyridine and N,N-dimethylformamide. Thereaction may be carried out at 50°-150° C. for 1-6 hours.

The β-oxoacetal derivative (IV) and the base may be used in amounts ofabout 1 to 1.5 equivalents and about catalytic amount to 2.5equivalents, respectively, to 1 equivalent of the picoline amidinederivative (III) or its salt.

After the reaction is lower, the reaction mixture is treated in a usualmanner, such as concentration under reduced pressure, if necessary,chromatography to obtain the pyridinylpyrimidine derivative (II).

Procedure (b):

A pyridinylpyrimidine derivative (II) is obtained by reductivedehalogenation of a halopyrimidine derivative of the formula: ##STR6##wherein R₁, R₂, R₃, R₄, R₅ and n are the same as defined above and X ishalogen.

The dehalogenation is, for example, carried out, in the presence of acatalyst such as palladium carbon, under hydrogen gas in an inertsolvent such as water, lower alcohol (e.g. methanol or ethanol),ethylacetate, toluene or a mixture thereof.

In this procedure, it is preferable to use of hydrogen gas having apressure of a range from 1 to 3 atom.

The procedure may be conducted in the presence of a dehydrohalogenatingagent, such as a base (e.g., ammonia, sodium hydroxide, sodiumcarbonate, sodium acetate) or basic ion exchange resin (e.g., "Dowex"®(a product of Dow Chemical Co.)).

The reaction may be carried out at room temperature to 50° C. for 0.5-3hours.

After the reaction is over, the reaction mixture is filtered to removethe waste catalyst, and the filtrate is concentrated in vacuo to give aresidue. Then, when no dehydrohalogenating agent is used, aqueoussolution of an inorganic base is added to the residue and the mixture isextracted with an organic solvent, while, when the dehydrohalogenatingagent is used, water is added to the residue and the mixture isextracted with an organic solvent.

Then, the extract obtained above is treated in a usual manner such asconcentration and further, if necessary, chromatography.

Procedure (c):

A pyridinylpyrimidine derivative of the formula: ##STR7## wherein R₁,R₂, R₃, R₄, R₅ and n are the same as defined above and R₆ " is loweralkoxy or lower alkylthio, is obtained by allowing the halopyrimidinederivative (V) to react with an alkali metal compound of the formula:

    R.sub.6 "Y                                                 (VII)

wherein R₆ " is defined above and Y is alkali metal.

Examples of the alkali metal are sodium, potassium, etc.

The reaction may be carried out at 10°-120° C. for 1 to 48 hours.

The alkali metal compound (VII) is usually used in an amount of about 1to 1.5 equivalents to 1 equivalent of the halopyrimidine derivative (V).

The reaction is usually carried out in the presence of a solvent such asan alcohol, an ether and a mixture thereof.

In case of using the alkali metal compound wherein R₆ " is lower alkoxy,the corresponding alcohol to R₆ " moiety (e.g., methanol or ethanol),ether (e.g. diethyl ether, dioxane or tetrahydrofuran) or a mixturethereof is used as the solvent. In case of using the alkali metalcompound wherein R₆ " is lower alkylthio, ether (e.g. diethylether,dioxane or tetrahydrofuran), nitrile (e.g. acetonitrile), aromatichydrocarbon (e.g. toluene) water or a mixture thereof is used as thesolvent.

After the reaction is over, the reaction mixture is concentrated invacuo. The residue obtained is subjected to a usual post-treatment suchas extraction with organic solvent, concentration, and if necessary,chromatography to obtain the objective compound (VI).

Procedure (d):

A pyridinylpyrimidine derivative of the formula: ##STR8## wherein R₁,R₂, R₃, R₄, R₅ and n are the same as defined above and R₆ "' is loweralkyl, is obtained by allowing the halopyrimidine derivative (V) toreact, in the presence of a base, with a diester derivative of theformula:

    R.sub.8 CH(COOR.sub.9).sub.2                               (IV)

wherein R₈ is hydrogen, methyl or ethyl and R₉ is lower alkyl, followedby hydrolysis and decarbonation.

Examples of the base are alkali metal hydride (e.g. sodium hydride),alkyl lithium (e.g. n-butyl lithium), lithium dialkylamide (e.g. lithiumdiisopropylamide (LDA)) and alkali metal hydroxide (e.g. sodiumhydroxide).

The reaction may be carried out at 0°-150° C. for 0.5-24 hours.

The diester derivative (IX) and the base are usually used in amounts of1 to 2 equivalents, respectively, to 1 equivalent of the halopyrimidinederivative (V).

The reaction is usually carried out in the presence of an inert solvent(e.g. nitriles such as acetonitrile; ethers such as diethylether ortetrahydrofuran; halohydrocarbons such as chloroform; aromatichydrocarbons such as benzene or toluene; haloaromatic hydrocarbons suchas chlorobenzene; ketones such as acetone or methylisobutyl ketone;esters such as ethylacetate; sulfur compounds such as dimethylsulfoxideand sulfolane or mixture thereof).

After the reaction is over, the reaction mixture is subjected to ahydrolysis reaction and a decarbonation reaction to obtain thepyridinylpyrimidine derivative (VIII). The hydrolysis and thedecarbonation are typically carried out in the manner as shown below.

To the reaction mixture is added 2.1 to 5 equivalents of the base to 1equivalent of the halopyrimidine derivative (V) in the form of anaqueous solution or an aqueous lower alcohol (e.g. methanol or ethanol)solution at 10°-100° C. for a period from 10 minutes to 24 hours.Examples of the base are alkali metal hydroxide (e.g. sodium hydroxide)and alkali metal carbonate (e.g. sodium carbonate).

Into the reaction mixture obtained above is added 2.5 to 6 equivalentsof acid to 1 equivalent of the used halopyrimidine derivative (V) forthe decarbonation reaction. The decarbonation reaction may be carriedout at 20°-150° C. for a period from 10 minutes to 24 hours.

Examples of the acid are inorganic acid such as sulfuric acid orhydrochloric acid and organic acid such as acetic acid.

After the reaction is over, the reaction mixture is firstly neutralizedwith alkali metal hydroxide such as sodium hydroxide, alkaline earthmetal hydroxide such as calcium hydroxide, alkali metal carbonate suchas sodium carbonate or sodium bicarbonate, or organic base such astriethylamine.

Then, the reaction mixture is treated in a usual manner such asconcentration and extraction, if necessary, recrystallization and columnchromatography to obtain the pyridinylpyrimidine derivative (VIII).

Procedure (e):

A pyridinylpyrimidine derivative of the formula: ##STR9## wherein R₁,R₂, R₃, R₅ and n are the same as defined above and R₄ ' and R₆ ' areeach hydrogen, is obtained by allowing a picoline amidine derivative(III) or a salt thereof, to react with acetal derivative of the formula:##STR10## wherein R₁₀ is lower alkyl.

The reaction may be carried out at 50°-150° C. for 1-6 hours, in theabsence of a solvent.

The acetal derivative (XI) may be used in an amount of about 1 to 3equivalents to 1 equivalent of the picoline amidine derivative (III) ora salt thereof.

After the reaction is over, the reaction mixture is treated in a usualmanner, such as concentration under reduced pressure, if necessary,chromatography to obtain the pyridinylpyrimidine derivative (X).

When R₅ and R₆ in the formula (I) are halogen and hydrogen,respectively, the present compound having the formula (I) is obtained bya method disclosed in "Synthesis", March 1984, pp. 253-4.

The present compound having the formula (I) is easily converted to saltsthereof by allowing the compound to react with strong acid such ashydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.

The salt is typically obtained by the procedures shown below. Thecompound of the formula (I) is dissolved in a solvent and then oneequivalent of the acid in the form of gas or aqueous solution is addedthereto under ice cooling or at room temperature. After being left tostand for 10 minutes to one hour, the solution is subjected to apost-treatment such as concentration under reduced pressure, and ifnecessary recrystallization. Examples of the solvent are lower alcoholsuch as methanol or ethanol; aromatic hydrocarbon such as toluene orbenzene; ether such as ethyl ether, tetrahydrofuran or dioxane;halogenated hydrocarbon such as chloroform; ketone such as acetone;ester such as ethyl acetate; hydrocarbon such as hexane; water or amixture thereof.

Picoline amidine derivative of the formula (III) and halopyrimidinederivative of the formula (V) are typically prepared by the followingreaction scheme: ##STR11## wherein R₁, R₂, R₃, R₄, R₅ and n are the sameas defined above, R₁₁ and R₁₂ each represent lower alkyl and M is alkalimetal.

An imidate derivative of the formula (XIV) is prepared by allowing acyanopyridine derivative of the formula (XII), which is prepared by amethod described in J. Org. Chem., 48, 1375-1377 (1983), to react withan alkoxide of the formula (XIII). The picoline amidine of the formula(III) is prepared by allowing the imidate derivative of the formula(XIV) to react with an ammonium salt, followed by the decomposition of asalt of the amidine derivative of the formula (III) obtained. Ahydroxypyrimidine derivative of the formula (XVI) is obtained byallowing the picoline amidine derivative of the formula (III) or a saltthereof to react, in the presence of a base, with a β-oxocarboxylate ofthe formula (XV). The halopyrimidine derivative of the formula (V) isobtained by allowing the hydroxypyrimidine derivative of the formula(XVI) to react with a halogenating agent.

Details of the above production are as follows.

A reaction between the compound of the formula (XII) and the compound ofthe formula (XIII):

Examples of alkali metal atom in the alkoxide (XIII) are a sodium atom,a potassium atom, etc. The reaction is usually carried out in thepresence of a solvent at 10° to 50° C. for 1 to 48 hours. The alkoxide(XIII) may be used in an amount of 0.1 to 1 equivalent to 1 equivalentof the cyanopilidine derivative (XII). As the solvent, there may beused, for example, a lower alcohol corresponding to R₁₁ of the alkoxide(XIII), (e.g. methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropylalcohol or n-butyl alcohol), preferably methyl alcohol or ethyl alcohol.

After the reaction is over, neutralization of the solution is effectedwith acid, concentrated under reduced pressure and dissoved in anorganic solvent. After insoluble alkali metal salt is filtered out, thefiltrate is concentrated in vacuo, and, if necessary, distilled toobtain the imidate derivative (XIV).

A reaction between the compound (XIV) and ammonium salt:

In the step, ammonium salt used is that of, for example, hydrochloricacid, hydrobromic acid, acetic acid or formic acid.

The reaction is usually carried out in the presence of a solvent at30°-100° C. for 0.5-5 hour. The ammonium salt may be used in amounts of1 to 1.1 equivalents to 1 equivalent of the imidate derivative (XIV). Asthe solvent, there may be used, for instance, a lower alcohol,preferably a solution of ethanol or water.

After the reaction is over, the reaction mixture may be concentrated invacuo and, if necessary recrystallized to obtain such salt ashydrochloride, hydrobromide, acetate or formate of picoline amidinederivative of the formula (III). The salt is decomposed by a usualmanner such as neutralization with an inorganic base, for example sodiumhydroxide, potassium hydroxide, sodium methoxide of sodium ethoxide, toobtain picoline amidine derivative of the formula (III).

Alternatively, the salt may be subjected, as it is, to the next stepwhere decomposition thereof is effected.

Reaction between picoline amidine derivative having the formula (III) ora salt thereof and the β-oxocarboxylate having the formula (XV):

The reaction is usually carried out in the presence of a solvent at50°-150° C. for 1-24 hours. The β-oxocarboxylate (XV) may be used in anamount of 1 to 1.5 equivalents to 1 equivalent of the picoline amidinederivative (III) or a salt thereof. The base may be used from acatalytic amount to 1.5 equivalents to 1 equivalent of the picolineamidine derivative (III) or a salt thereof.

As the solvent, there may be used, for instance, lower alcohol such asmethanol or ethanol, cyclic ether such as dioxane, tetrahydrofuran,pyridine, N,N-dimethylformamide, water or a mixture thereof.

As the base, there may be used, for instance, inorganic base such assodium hydroxide, potassium hydroxide, potassium carbonate, or organicone such as alkali metal alkoxide such as sodium methoxide,triethylamine or N,N-diethylaniline. After the reaction is over, in caseof using the salt of picoline amidine derivative of the formula (III),the by-produced inorganic salt is filtered out, and the filtrate isconcentrated in vacuo to obtain a residue. The residue may be treated bychromatography or recrystallization to obtain the hydroxypyrimidinederivative (XVI).

Reaction between the hydroxypyrimidine derivative having the formula(XVI) and the halogenating agent:

As the halogenating agent, there may be used, for instance, thionylchloride, phosgene, phosphoryl chloride, phosphorus pentachloride,phosphoryl bromide or phosphorus tribromide.

The reaction is usually carried out in the presence of a solvent at50°-150° C. for 1-10 hours. The halogenating agent may be used in anamount of 1 to 10 equivalents to 1 equivalent of the hydroxypyrimidinederivative (XVI). As the solvent, there may be used, for instance,aromatic hydrocarbons (e.g. benzene or toluene), halogenatedhydrocarbons (e.g. chlorobenzene), etc.

After the reaction is over, a post-treatment of the reaction mixture maybe carried out in a usual manner. For instance, the reaction mixture isconcentrated under reduced pressure and neutralized with an inorganicbase (e.g. sodium hydroxide). Then, the above mixture is extracted withan organic solvent and the extract is concentrated in vacuo to obtainthe halopyrimidine derivative (V). Any further procedure such aschromatography or recrystallization may be applied, if necessary, to theresultant product.

The pyridinyl pyrimidine derivatives of this invention may be used as anactive ingredient of a plant disease protectant, and it is usually mixedwith a solid carrier, a liquid carrier, a surface active agent, andother adjuvants and formulated into emulsion, wettable powder,suspension, granule, dust, or liquid.

These formulations may contain the pyridinylpyrimidine derivative in aconcentration of about 0.1 to 99% by weight, preferably about 0.2 to 95%by weight.

Examples of solid carriers include kaolin clay, attapulgite clay,bentonite, Japanese acid clay, pyrophyllite, talc, diatomaceous earth,calcite, corncob powder, walnut shell powder, urea, ammonium sulfate,and synthetic hydrated silica, which are in the form of finely dividedpowder or granule. Examples of liquid carrier include aromatichydrocarbons, e.g., xylene and methylnaphthalane; alcohols, e.g.,isopropanol, ethylene glycol, and cellosolve; ketones, e.g., acetone,cyclohexanone, and isophorone; vegetable oils e.g., soybean oil andcottonseed oil; dimethylsulfoxide, acetonitrile or water.

Examples of surface active agents for emulsification, dispersion, andwetting include anionic surface active agents such as alkyl sulfatesalt, alkyl or aryl sulfonate, dialkylsulfosuccinate, polyoxyethylenealkylarylether, phosphate salt, and naphthalene sulfonic acid-formalincondensate; and nonionic surface active agents such as polyoxyethylenealkyl ether, polyoxyethylene-polyoxypropylene block copolymer,sorbitan-fatty acid ester or polyoxyethylene-sorbitan fatty acid ester.Examples of adjuvants include ligninsulfonate, alginate, polyvinylalcohol, gum arabic, CMC (carboxymethylcellulose) or PAP (isopropylacidphosphate).

These formulations are used as such or after dilution with water forfoliage application or soil treatment or soil incorporation. They mayalso be used in combination with other plant disease protectants fortheir enhanced control effect. Further, they may be used in combinationwith an insecticide, acaricide, nematicide, herbicide, plant growthregulator, fertilizer, and soil conditioner.

In the case where the present compound is used as an active ingredientof a plant disease protectant, the dosage varies depending on theweather conditions, formulation, application time, application method,application place, object diseases, and object crops. The dosage isusually 0.2 to 200 g, preferably 1 to 100 g for an area of 1 are. In thecase of emulsion, wettable powder, suspension, or liquid formulationwhich is diluted with water prior to application, the concentrationshould be 0.005 to 0.5%, preferably 0.01 to 0.2% by weight. Granules anddusts are used as such without dilution.

The present invention is explained in further detail referring tosynthesis examples, formulation examples and efficiency tests.

SYNTHESIS EXAMPLES OF THE PRESENT COMPOUND Example 1

To the mixture of 6-m-chlorophenyl-2-picoline amidine hydrochloride (1g) and methanol (50 ml) were added 28% sodium methoxide solution inmethanol (1.08 g) and 1,1-dimethoxy-3-butanone (purity 90%, 0.7 g). Themixture was heated under refluxing for an hour, and was left to stand atroom temperature. After the insoluble salt was filtered off, thereaction solution was concentrated under reduced pressure.

The residue obtained was subjected to silica gel column chromatography(eluent; n-hexane:acetone=2:1 in volume) to obtain2-(6-chlorophenyl-2-pyridinyl)-4-methyl pyrimidine (0.86 g, yield 82%).

n_(D) ²³ 1.6363.

PMR (CDCl₃) δppm: 2.60 (s, 3H, --CH₃) 7.06 (d, 1H, pyrimidine-H⁵, J=5.4Hz), 8.67 (d, 1H, pyrimidine-H⁶, J=5.4 Hz).

EXAMPLE 2

To a solution of4-chloro-6-methyl-2-(5-methyl-6-phenyl-2-pyridinyl)pyrimidine (1 g) intoluene (10 ml) and ethylalcohol (5 ml), were added a sodium carbonate(0.25 g) solution in water (2 ml), and then 5% palladium carbon (0.1 g).

The mixture was brought into contact with hydrogen gas for 30 minutes.After palladium carbon was filtered off, water (20 ml) was added andthen extracted with toluene (30 ml). After the extract was dried overanhydrous magnesium sulfate, it was concentrated under reduced pressureto obtain 4-methyl-2-(5-methyl-6-phenyl-2-pyridinyl)pyrimidine (0.85 g,yield 96%)

m.p. 104.8° C.

PMR (CDCl₃) δppm: 2.36 (s, 3H, --CH₃), 2.59 (s, 3H, --CH₃), 7.05 (d, 1H,pyrimidine-H⁵, J=5.4 Hz), 8.28 (d, 1H, pyridine-H³, J=7.2 Hz), 8.67 (d,1H, pyrimidine-H⁶, J=5.4 Hz).

EXAMPLE 3

To 4-chloro-6-methyl-2-(6-o-tolyl-2-pyridinyl)pyrimidine (2 g) was addedsodium methoxide prepared from methanol (10 ml) and metallic sodium(0.19 g). After the mixture was left to stand at room temperature for 30minutes, water (30 ml) and chloroform (100 ml) was added thereto, andthen extracted. After the extract was dried over anhydrous magnesiumsulfate, it was concentrated under reduced pressure to obtain4-methoxy-6-methyl-2-(6-o-tolyl-2-pyridinyl)pyrimidine (1.9 g, yield96%).

m.p. 102.8° C.

PMR (CDCl₃) δppm: 2.51 (s, 6H, --CH₃), 4.03 (s, 3H, --OCH₃), 6.51 (s,1H, pyrimidine-H⁵), 7.79 (t, 1H, pyridine-H⁴, J=7.2 Hz), 8.34 (d, 1H,pyridine-H³, J=7.2 Hz).

EXAMPLE 4

To tetrahydrofuran (30 ml) were added diethylmalonate (1.6 g) and 60%oily sodium hydride (0.4 g), and then4-chloro-6-methyl-2-(6-phenyl-2-pyridinyl)pyrimidine (2 g). The mixturewas heated under refluxing for 30 minutes. Sodium hydroxide (0.85 g)solution in water (10 ml) and methanol (10 ml) was added thereto, andthe mixture was further heated under refluxing for 20 minutes. After themixture was left to stand until it was cooled to room temperature,sulfuric acid (1.4 g) was added dropwise thereto. The mixture was heatedunder refluxing for 30 minutes and left to stand to room temperature.1-N aqueous sodium carbonate solution was added until a mixture wasneutralized, and concentrated under reduced pressure. The residue wassubjected to silica-gel column chromatography (eluent;n-hexane:acetone=3:1 in volume) to give4,6-dimethyl-2-(6-phenyl-2-pyridinyl)pyrimidine (1.6 g, yield 86%).

m.p. 117.0° C.

PMR (CDCl₃) δppm: 2.53 (s, 6H,, --CH₃), 6.92 (s, 1H, pyrimidine-H⁵).

EXAMPLE 5

To 6-phenyl-2-picoline amidine hydrochloride (1 g) was addedmalonaldehyde bis(dimethylacetal) (2.1 g).

The mixture was heated about 120° C. for an hour, and then concentratedunder reduced pressure.

The residue obtained was subjected to silica gel column chromatography(eluent; n-hexane:acetone=1:1 in volume) to obtain2-(6-phenyl-2-pyridinyl)pyrimidine (0.7 g, yield 70%).

PMR (CDCl₃) δppm: 7.11 (t, 1H, pyrimidine-H⁵, J=4.8 Hz), 8.76 (d, 2H,pyrimidine-H⁴ and H⁶, J=4.8 Hz).

Some of compounds of this invention which are prepared according to thesimilar procedures to the above are listed in Table 1.

                                      TABLE 1                                     __________________________________________________________________________    Pyridinylpyrimidine derivatives or salts thereof                               ##STR12##                                                                     numberCompound                                                                       ##STR13##                                                                               R.sub.2                                                                           R.sub.3                                                                           R.sub.4                                                                           R.sub.5                                                                           R.sub.6                                                                           constantPhysical                        __________________________________________________________________________     (1)                                                                                  ##STR14##                                                                              H   H   H   H   H   m.p. 132.1° C.                     (2)                                                                                  ##STR15##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 123.9° C.                     (3)                                                                                  ##STR16##                                                                              H   H   CH.sub.3                                                                          H   OC.sub.2 H.sub.5                                                                  n.sub.D.sup. 28 1.6185                    (4)                                                                                  ##STR17##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 117.0° C.                     (5)                                                                                  ##STR18##                                                                              H   H   CH.sub.3                                                                          H   C.sub.2 H.sub.5                                                                   m.p. 90.2° C.                      (6)                                                                                  ##STR19##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 62.5° C.                      (7)                                                                                  ##STR20##                                                                              H   H   CH.sub.3                                                                          H   SCH.sub.3                                                                         n.sub.D.sup.25 1.6566                     (8)                                                                                  ##STR21##                                                                              H   H   CH.sub.3                                                                          CH.sub.3                                                                          OCH.sub.3                                                                         m.p. 126.0° C.                     (9)                                                                                  ##STR22##                                                                              H   H   CH.sub.3                                                                          CH.sub.3                                                                          H   n.sub.D.sup.25.5 1.6232                  (10)                                                                                  ##STR23##                                                                              H   H   n-C.sub.3 H.sub.7                                                                 H   OCH.sub.3                                                                         n.sub.D.sup.24 1.6072                    (11)                                                                                  ##STR24##                                                                              H   H   n-C.sub.3 H.sub.7                                                                 H   H   n.sub.D.sup.27.5 1.6107                  (12)                                                                                  ##STR25##                                                                              H   H   ( CH.sub.2 ) .sub.4                                                                   OCH.sub.3                                                                         m.p. 127.4° C.                    (13)                                                                                  ##STR26##                                                                              H   H   (CH.sub.2 ) .sub.4                                                                    H   m.p. 130.4° C.                    (14)                                                                                  ##STR27##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 89.3° C.                     (15)                                                                                  ##STR28##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          H   H   m.p. 104.8° C.                    (16)                                                                                  ##STR29##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          CH.sub.3                                                                          OCH.sub.3                                                                         m.p. 150.6° C.                    (17)                                                                                  ##STR30##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          CH.sub.3                                                                          CH.sub.3                                                                          m.p. 155.7° C.                    (18)                                                                                  ##STR31##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          CH.sub.3                                                                          H   m.p. 163.0° C.                    (19)                                                                                  ##STR32##                                                                              H   t-C.sub.4 H.sub.9                                                                 CH.sub.3                                                                          H   H   m.p. 106.1° C.                    (20)                                                                                  ##STR33##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 102.8° C.                    (21)                                                                                  ##STR34##                                                                              H   H   CH.sub.3                                                                          H   OC.sub.2 H.sub.5                                                                  n.sub.D.sup.23 1.5883                    (22)                                                                                  ##STR35##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          n.sub.D.sup.23 1.6055                    (23)                                                                                  ##STR36##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.25 1.6129                    (24)                                                                                  ##STR37##                                                                              CH.sub.3                                                                          H   H   H   H   m.p. 129.4° C.                    (25)                                                                                  ##STR38##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          H   H   m.p. 81.0° C.                     (26)                                                                                  ##STR39##                                                                              H   CH.sub.3                                                                          CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 119.6° C.                    (27)                                                                                  ##STR40##                                                                              H   CH.sub.3                                                                          CH.sub.3                                                                          H   H   n.sub.D.sup.27.5 1.5928                  (28)                                                                                  ##STR41##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         n.sub.D.sup.24 1.6031                    (29)                                                                                  ##STR42##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         n.sub.D.sup.25 1.5823                    (30)                                                                                  ##STR43##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 138.2° C.                    (31)                                                                                  ##STR44##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.25.5 1.6360                  (32)                                                                                  ##STR45##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 127.6° C.                    (33)                                                                                  ##STR46##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 156.1° C.                    (34)                                                                                  ##STR47##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 132.0° C.                    (35)                                                                                  ##STR48##                                                                              CH.sub.3                                                                          H   H   H   H   m.p. 144.6° C.                    (36)                                                                                  ##STR49##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          H   H   m.p. 153.8° C.                    (37)                                                                                  ##STR50##                                                                              H   H   H   H   H   n.sub.D.sup.25 1.6167                    (38)                                                                                  ##STR51##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         n.sub.D.sup.24 1.5862                    (39)                                                                                  ##STR52##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.27.5 1.6049                  (40)                                                                                  ##STR53##                                                                              H   H   H   H   H   m.p. 138.6° C.                    (41)                                                                                  ##STR54##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 119.1° C.                    (42)                                                                                  ##STR55##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 129.0° C.                    (43)                                                                                  ##STR56##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 129.1° C.                    (44)                                                                                  ##STR57##                                                                              H   H   H   H   H   m.p. 120.8° C.                    (45)                                                                                  ##STR58##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 142.5° C.                    (46)                                                                                  ##STR59##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 123.9° C.                    (47)                                                                                  ##STR60##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          n.sub.D.sup.25 1.6010                    (48)                                                                                  ##STR61##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 116.2° C.                    (49)                                                                                  ##STR62##                                                                              CH.sub.3                                                                          H   H   H   H   m.p. 128.7° C.                    (50)                                                                                  ##STR63##                                                                              CH.sub.3                                                                          H   CH.sub.3                                                                          H   H   m.p. 114.9° C.                    (51)                                                                                  ##STR64##                                                                              H   CH.sub.3                                                                          CH.sub.3                                                                          H   H   m.p. 84.2° C.                     (52)                                                                                  ##STR65##                                                                              H   CH.sub.3                                                                          CH.sub.3                                                                          CH.sub.3                                                                          H   n.sub.D.sup.17 1.6054                    (53)                                                                                  ##STR66##                                                                              H   CH.sub.3                                                                          CH.sub.3                                                                          Cl  H   m.p. 106.4° C.                    (54)                                                                                  ##STR67##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 138.7° C.                    (55)                                                                                  ##STR68##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.23 1.6363                    (56)                                                                                  ##STR69##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 114.0° C.                    (57)                                                                                  ##STR70##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 157.5° C.                    (58)                                                                                  ##STR71##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 95.2° C.                     (59)                                                                                  ##STR72##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 63.7° C.                     (60)                                                                                  ##STR73##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 169.3° C.                    (61)                                                                                  ##STR74##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 138.1° C.                    (62)                                                                                  ##STR75##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 145.5° C.                    (63)                                                                                  ##STR76##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         m.p. 91.8° C.                     (64)                                                                                  ##STR77##                                                                              H   H   CH.sub.3                                                                          H   CH.sub.3                                                                          m.p. 104.1° C.                    (65)                                                                                  ##STR78##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 91.7° C.                     (66)                                                                                  ##STR79##                                                                              H   H   H   H   H   n.sub.D.sup.25 1.5892                    (67)                                                                                  ##STR80##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         n.sub.D.sup.29 1.5862                    (68)                                                                                  ##STR81##                                                                              H   H   CH.sub.3                                                                          H   C.sub.2 H.sub.5                                                                   n.sub.D.sup.24 1.5478                    (69)                                                                                  ##STR82##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.29 1.6768                    (70)                                                                                  ##STR83##                                                                              H   H   CH.sub.3                                                                          H   OCH.sub.3                                                                         n.sub.D.sup.24 1.6092                    (71)                                                                                  ##STR84##                                                                              H   H   CH.sub.3                                                                          H   H   n.sub.D.sup.27.5 1.6135                  (72)                                                                                  ##STR85##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 81.2° C.                     (73)                                                                                  ##STR86##                                                                              H   H   CH.sub.3                                                                          H   H   m.p. 108.3° C.                    (74)   HCl salt of compound No. 6    m.p. 180.9° C.                    (75)   1/2.H.sub.2 SO.sub.4 salt of compound No. 6                                                                 m.p. 179.1° C.                    (76)   HNO.sub.3 salt of compound No. 6                                                                            m.p. 120.5° C.                    __________________________________________________________________________

The following reference examples show the preparation of variousstarting compounds.

REFERENCE EXAMPLE 1 Preparation of picoline amidine derivative (III)(HCl-salt)

2-Cyano-6-phenylpyridine (20 g) was dissolved in a solution of sodiummethoxide in methanol prepared from methanol (200 ml) and metallicsodium (0.77 g). After the solution was left to stand overnight, aceticacid (2.0 g) was added thereto, followed by concentration under reducedpressure. The resulting residue was dissolved in ether (200 ml) andinsoluble materials were filtered out. The filtrate was concentratedunder reduced pressure to obtain methyl 2-picoline imidate.

To the imidate obtained above was added a solution of ammonium chloride(5.94 g) in water (30 ml) and ethanol (120 ml) and the mixture washeated under refluxing for one hour. After being left to stand to cool,the reaction mixture was concentrated under reduced pressure. Thecrystalline residue obtained was washed with acetone to obtain6-phenyl-2-picoline amidine hydrochloride (22 g).

m.p. 166.5° C.

Some of picoline amidine derivatives or salts thereof having the formula(III) which are able to prepare according to the similar procedure tothe above are listed in Table 2.

                  TABLE 2                                                         ______________________________________                                        Picoline amidine derivatives or their salts                                    ##STR87##                                                                     ##STR88##    R.sub.2                                                                              R.sub.3                                                                               Physical constant                                ______________________________________                                         ##STR89##   H      H       m.p. 166.5° C. (HCl salt)                   ##STR90##   CH.sub.3                                                                             H       m.p. 259.0° C. (HCl salt)                   ##STR91##   H      t-C.sub.4 H.sub.9                                                                     m.p. 277.0° C. (HCl salt)                   ##STR92##   H      H       m.p. 194.0° C.                              ##STR93##   H      H       m.p. 209.5° C. (HCl salt)                   ##STR94##   CH.sub.3                                                                             H       m.p. 271.0° C. (HCl salt)                   ##STR95##   H      CH.sub.3                                                                              m.p. 248.0° C. (HCl salt)                   ##STR96##   H      H       m.p. 243.5° C. (HCl salt)                   ##STR97##   H      H       m.p. 192.0° C. (HCl salt)                   ##STR98##   H      H       m.p. 224.0° C. (HCl salt)                   ##STR99##   CH.sub.3                                                                             H       m.p. 276.5° C. (HCl salt)                   ##STR100##  H      H       m.p. 254.0° C. (HCl salt)                   ##STR101##  H      H       m.p. 300° C. or more (HCl salt)             ##STR102##  H      H       m.p. 246.5° C. (HCl salt)                   ##STR103##  H      H       m.p. 246.1° C. (HCl salt)                   ##STR104##  CH.sub.3                                                                             H       m.p. 266.5° C. (HCl salt)                   ##STR105##  H      CH.sub.3                                                                              m.p. 237.0° C. (HCl salt)                   ##STR106##  H      H       m.p. 169.8° C. (HCl salt)                   ##STR107##  H      H       m.p. 266.6° C. (HCl salt)                   ##STR108##  H      H       m.p. 255.5° C. (HCl salt)                   ##STR109##  H      H       m.p. 248.2° C. (HCl salt)                   ##STR110##  H      H       m.p. 122.8° C. (HCl salt)                   ##STR111##  H      H       m.p. 290.9° C. (HCl salt)                   ##STR112##  H      H       m.p. 180.7° C. (HCl salt)                   ##STR113##  H      H       m.p. 181.5° C. (HCl salt)                   ##STR114##  H      H       m.p. 232.7° C. (HCl salt)                   ##STR115##  H      H       m.p. 147.5° C. (HCl salt)                  ______________________________________                                    

REFERENCE EXAMPLE 2 Preparation of hydroxypyrimidine derivative (XVI)

6-Phenyl-2-picoline amidine hydrochloride (4 g) was dissolved in asolution of sodium ethoxide in ethanol prepared from ethanol (100 ml)and metallic sodium (0.47 g).

Ethyl acetoacetate (2.45 g) was added to the solution obtained above,then the mixture was heated under refluxing for 1 hour. After thereaction mixture was cooled to room temperature, it was neutralized withacetic acid and then concentrated under reduced pressure. The residueobtained was washed with water and n-hexane to obtain4-hydroxy-6-methyl-2-(6-phenyl-2-pyridinyl)pyrimidine (3.96 g, yield88%).

m.p. 172.2° C.

PMR (CDCl₃) δppm: 2.37 (s, 3H, --CH₃), 6.29 (s, 1H, pyrimidine-H⁵).

Some of hydroxypyrimidine derivatives (XVI) according to the similarprocedure to the above are listed in Table 3.

                  TABLE 3                                                         ______________________________________                                        Hydroxypyrimidine derivatives                                                  ##STR116##                                                                    ##STR117##   R.sub.2                                                                              R.sub.3                                                                              R.sub.4                                                                             R.sub.5                                                                            constantPhysical                       ______________________________________                                         ##STR118##  H      H      CH.sub.3                                                                            H    m.p. 172.2° C.                    ##STR119##  H      H      CH.sub.3                                                                            CH.sub.3                                                                           m.p. 193.2° C.                    ##STR120##  H      H      n-C.sub.3 H.sub.7                                                                   H    m.p. 203.0° C.                    ##STR121##  H      H      (CH.sub.2) .sub.4                                                                      m.p. 184.2° C.                      ##STR122##  CH.sub.3                                                                             H      CH.sub.3                                                                            H    m.p. 183.6° C.                    ##STR123##  CH.sub.3                                                                             H      CH.sub.3                                                                            CH.sub.3                                                                           m.p. 164.3° C.                    ##STR124##  H      H      CH.sub.3                                                                            H    m.p. 173.1° C.                    ##STR125##  H      CH.sub.3                                                                             CH.sub.3                                                                            H    m.p. 234.6° C.                    ##STR126##  H      H      CH.sub.3                                                                            H    m.p. 114.3° C.                    ##STR127##  H      H      CH.sub.3                                                                            H    m.p. 163.4° C.                    ##STR128##  H      H      CH.sub.3                                                                            H    m.p. 258.0° C.                    ##STR129##  H      H      CH.sub.3                                                                            H    m.p. 173.7° C.                    ##STR130##  H      H      CH.sub. 3                                                                           H    m.p. 164.5° C.                    ##STR131##  H      H      CH.sub.3                                                                            H    m.p. 219.0° C.                    ##STR132##  H      CH.sub.3                                                                             CH.sub.3                                                                            CH.sub.3                                                                           m.p. 128.4° C.                    ##STR133##  H      CH.sub.3                                                                             CH.sub.3                                                                            Cl   m.p. 139.0° C.                    ##STR134##  H      H      CH.sub.3                                                                            H    m.p. 189.6° C.                    ##STR135##  H      H      CH.sub.3                                                                            H    m.p. 231.0° C.                    ##STR136##  H      H      CH.sub.3                                                                            H    m.p. 184.1° C.                    ##STR137##  H      H      CH.sub.3                                                                            H    m.p. 222.5° C.                    ##STR138##  H      H      CH.sub.3                                                                            H    m.p. 193.1° C.                   ______________________________________                                    

REFERENCE EXAMPLE 3 Preparation of halopyrimidine derivative (V)

To solution of 4-hydroxy-6-methyl-2-(6-m-tolyl-2-pyridinyl)pyrimidine (5g) in toluene (100 ml), was added phosphoryl chloride (5 g). The mixturewas heated under refluxing for one hourand left to stand to roomtemperature. Aqueous sodium carbonate solution was added thereto untilthe reaction solution became about pH 8 to be separated into two layers.Toluene layer was washed with water and dried over anhydrous magnesiumsulfate. The toluene layer was concentrated under reduced pressure toobtain 4-chloro-6-methyl-2-(6-m-tolyl-2-pyridinyl)pyrimidine (4.9 g,yield 92%).

m.p. 104.9° C.

PMR (CDCl₃) δppm: 2.44 (s, 3H, --CH₃), 2.63 (s, 3H, --CH₃).

Some of halopyrimidine derivatives (V) prepared according to the similarprocedure to the above are listed in Table 4.

                  TABLE 4                                                         ______________________________________                                        Halopyrimidine derivatives                                                     ##STR139##                                                                    ##STR140##  R.sub.2 R.sub.3                                                                        R.sub.4                                                                               R.sub.5                                                                            X   constantPhysical                       ______________________________________                                         ##STR141## HH       CH.sub.3                                                                              H    Cl  m.p. 103.4° C.                    ##STR142## HH       CH.sub.3                                                                              CH.sub.3                                                                           Cl  m.p. 123.4° C.                    ##STR143## HH       n-C.sub.3 H.sub.7                                                                     H    Cl  m.p.  81.3° C.                    ##STR144## CH.sub.3 H                                                                             CH.sub.3                                                                              H    Cl  m.p. 128.5° C.                    ##STR145## CH.sub.3 H                                                                             CH.sub.3                                                                              CH.sub.3                                                                           Cl  m.p. 155.3° C.                    ##STR146## HH       CH.sub.3                                                                              H    Cl  resin                                    ##STR147## HCH.sub.3                                                                              CH.sub.3                                                                              H    Cl  m.p.  84.6° C.                    ##STR148## HH       CH.sub.3                                                                              H    Cl  n .sub.D.sup.24  1.6103                  ##STR149## HH       CH.sub.3                                                                              H    Cl  m.p. 104.9° C.                    ##STR150## HH       CH.sub.3                                                                              H    Cl  m.p. 138.5° C.                    ##STR151## HH       CH.sub.3                                                                              H    Cl  m.p.  60.7° C.                    ##STR152## HH       CH.sub.3                                                                              H    Cl  m.p. 129.1° C.                    ##STR153## HH       CH.sub.3                                                                              H    Cl  n  .sub.D.sup.29.5  1.6768               ##STR154## HCH.sub.3                                                                              CH.sub.3                                                                              CH.sub.3                                                                           Cl  m.p. 130.1° C.                    ##STR155## HCH.sub.3                                                                              CH.sub.3                                                                              Cl   Cl  m.p. 170.7° C.                    ##STR156## HH       CH.sub.3                                                                              H    Cl  m.p. 107.7° C.                    ##STR157## HH       CH.sub.3                                                                              H    Cl  m.p. 151.0° C.                    ##STR158## HH       CH.sub.3                                                                              H    Cl  m.p. 121.0° C.                    ##STR159## HH       CH.sub.3                                                                              H    Cl  m.p. 112.5° C.                    ##STR160## HH       CH.sub.3                                                                              H    Cl  m.p. 101.8° C.                    ##STR161## HH       CH.sub.3                                                                              H    Cl  m.p. 119.5° C.                   ______________________________________                                    

FORMULATION EXAMPLES

The present compounds used are identified by numbers shown in Table 1.Quantities are expressed by parts by weight.

FORMULATION EXAMPLE 1

A wettable powder each is prepared by mixing and pulverizing 50 parts ofeach of the present compounds (1)-(76), 3 parts of calciumligninsulfonate, 2 parts of sodium lauryl sulfate and 45 parts ofsynthetic hydrated silica.

FORMULATION EXAMPLE 2

A suspension each is prepared by mixing 25 parts of each of the presentcompounds (1)-(76), 3 parts of polyoxyethylene sorbitanmonooleate, 3parts of CMC and 69 parts of water, followed by wet grinding to give aparticle size smaller than 5 microns.

FORMULATION EXAMPLE 3

A dust each is prepared by mixing and pulverizing 2 parts of each of thepresent compounds (1)-(76), 88 parts of kaolin clay and 10 parts oftalc.

FORMULATION EXAMPLE 4

An emulsifiable concentrate each is prepared by thoroughly mixing 20parts of each of the present compounds (1)-(76), 14 parts ofpolyoxyethylene styrylphenyl ether, 6 parts of calciumdodecylbenzenesulfonate and 60 parts of xylene.

FORMULATION EXAMPLE 5

A granule each is prepared by mixing and pulverizing 2 parts of each ofthe present compounds (1)-(76), 1 part of synthetic hydrated silica, 2parts of calcium ligninsulfonate, 30 parts of bentonite, and 65 parts ofkaolin clay, followed by kneading with water, granulation and drying.

The following test examples demonstrate the effectiveness of the presentcompound used as an active ingredient of plant disease protectants. Thepresent compounds used in the test examples are identified by thecompound numbers shown in Table 1, and the compounds used for controlare identified by the compound symbols shown in Table 5.

                  TABLE 5                                                         ______________________________________                                        Com-                                                                          pound                                                                         symbol                                                                              Compound             Remarks                                            ______________________________________                                               ##STR162##          Commercial fungicide "IBP"                         B     --                   Commerical                                                                    fungicide                                                                     "Validamycin"                                      C                                                                                    ##STR163##          Commerical fungicide "MBC"                         D                                                                                    ##STR164##          Commerical fungicide "TPN"                         E                                                                                    ##STR165##          Commerical fungicide "Captafol"                    ______________________________________                                    

The controlling effect was evaluated by visually observing the degree offungus colony and infected area of the leaves and stems of the testplants. The results of evaluation were expressed in terms of six ratingsas follows:

"5" Not observed at all.

"4" Observed on about 10% of the leaves and stems.

"3" Observed on about 30% of the leaves and stems.

"2" Observed on about 50% of the leaves and stems.

"1" Observed on about 70% of the leaves and stems.

"0" Same as control.

TEST EXAMPLE 1

Test for preventive controlling effect on blast (Pyricularia oryzae) ofrice

Rice seeds (var.: Kinki No. 33) were sown in the sandy loam filled in aplastic pot. After raised for 20 days in a greenhouse, the seedlingswere subjected to foliage application with a spray liquid of thewettable powder prepared according to Formulation Example 1 which wasdiluted with water to the given concentrations. After application, theseedlings were air-dried and then inoculated with spores of Pyriculariaoryzae by spraying a suspension of spores. The inoculated seedlings weregrown in a dark damp place at 28° C. for 4 days, and the controllingeffect was examined. The results are shown in Table 6.

                  TABLE 6                                                         ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (1)        200             5                                                  (2)        200             5                                                  (3)        200             5                                                  (4)        200             5                                                  (5)        200             5                                                  (6)        200             5                                                  (7)        200             5                                                  (8)        200             5                                                  (9)        200             5                                                 (10)        200             5                                                 (11)        200             5                                                 (12)        200             5                                                 (13)        200             5                                                 (14)        200             5                                                 (15)        200             5                                                 (16)        200             5                                                 (17)        200             5                                                 (18)        200             5                                                 (19)        200             5                                                 (20)        200             5                                                 (21)        200             5                                                 (22)        200             5                                                 (23)        200             5                                                 (24)        200             5                                                 (25)        200             5                                                 (26)        200             5                                                 (27)        200             5                                                 (28)        200             5                                                 (29)        200             5                                                 (30)        200             5                                                 (31)        200             5                                                 (32)        200             5                                                 (33)        200             5                                                 (34)        200             5                                                 (35)        200             5                                                 (36)        200             5                                                 (37)        200             5                                                 (38)        200             5                                                 (39)        200             5                                                 (40)        200             5                                                 (41)        200             5                                                 (42)        200             5                                                 (43)        200             5                                                 (44)        200             5                                                 (45)        200             5                                                 (46)        200             5                                                 (47)        200             5                                                 (48)        200             5                                                 (49)        200             5                                                 (50)        200             5                                                 (51)        200             5                                                 (52)        200             5                                                 (53)        200             5                                                 (54)        200             5                                                 (55)        200             5                                                 (56)        200             5                                                 (57)        200             5                                                 (58)        200             5                                                 (59)        200             5                                                 (60)        200             5                                                 (61)        200             5                                                 (62)        200             5                                                 (63)        200             5                                                 (64)        200             5                                                 (65)        200             5                                                 (66)        200             5                                                 (67)        200             5                                                 (68)        200             5                                                 (69)        200             5                                                 (70)        200             5                                                 (71)        200             5                                                 (72)        200             5                                                 (73)        200             5                                                 (74)        200             5                                                 (75)        200             5                                                 (76)        200             5                                                 Reference   200             4                                                 compound A                                                                    ______________________________________                                    

TEST EXAMPLE 2

Test for curative controlling effect on blast (Pyricularia oryzae) ofrice

Rice seeds (var.: Kinki No. 33) were sown in the sandy loam filled in aplastic pot. After raising for 20 days in a greenhouse, the seedlingswere inoculated with spores of Pyricularia oryzae by spraying asuspension of spores. The inoculated seedlings were grown in a dark dampplace at 28° C. for 16 hours. The seedlings were subjected to foliageapplication with a spray liquid of the emulsion prepared according toFormulation Example 4 which was diluted with water to the givenconcentrations. After application, the seedlings were grown in a darkdamp place at 28° C. for 3 days, and the controlling effect wasexamined. The results are shown in Table 7.

                  TABLE 7                                                         ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (1)        200             5                                                  (2)        200             5                                                  (3)        200             5                                                  (4)        200             5                                                  (5)        200             5                                                  (6)        200             5                                                  (7)        200             5                                                  (8)        200             5                                                  (9)        200             5                                                 (10)        200             5                                                 (11)        200             5                                                 (12)        200             5                                                 (13)        200             5                                                 (14)        200             5                                                 (15)        200             5                                                 (16)        200             5                                                 (17)        200             5                                                 (18)        200             5                                                 (19)        200             5                                                 (20)        200             5                                                 (21)        200             5                                                 (22)        200             5                                                 (23)        200             5                                                 (24)        200             5                                                 (25)        200             5                                                 (26)        200             5                                                 (27)        200             5                                                 (28)        200             5                                                 (29)        200             5                                                 (30)        200             5                                                 (31)        200             5                                                 (32)        200             5                                                 (33)        200             5                                                 (34)        200             5                                                 (35)        200             5                                                 (36)        200             5                                                 (37)        200             5                                                 (38)        200             5                                                 (39)        200             5                                                 (40)        200             5                                                 (41)        200             5                                                 (42)        200             5                                                 (43)        200             5                                                 (44)        200             5                                                 (45)        200             5                                                 (46)        200             5                                                 (47)        200             5                                                 (48)        200             5                                                 (49)        200             5                                                 (50)        200             5                                                 (51)        200             5                                                 (52)        200             5                                                 (53)        200             5                                                 (54)        200             5                                                 (55)        200             5                                                 (56)        200             5                                                 (57)        200             5                                                 (58)        200             5                                                 (59)        200             5                                                 (60)        200             5                                                 (61)        200             5                                                 (62)        200             5                                                 (63)        200             5                                                 (64)        200             5                                                 (65)        200             5                                                 (66)        200             5                                                 (67)        200             5                                                 (68)        200             5                                                 (69)        200             5                                                 (70)        200             5                                                 (71)        200             5                                                 (72)        200             5                                                 (73)        200             5                                                 (74)        200             5                                                 (75)        200             5                                                 (76)        200             5                                                 Reference   200             4                                                 compound A                                                                    ______________________________________                                    

TEST EXAMPLE 3

Test for preventive controlling effect on sheath blight (Rhizoctoniasolani) of rice

Rice seeds (var.: Kinki No. 33) were sown in the sandy loam filled in aplastic pot. After raising for 28 days in a greenhouse, the seedlingswere subjected to foliage application with a spray liquid of thesuspension prepared according to Formulation Example 2 which was dilutedwith water to the given concentrations. After application, the seedlingswere air-dried and then inoculated with mycelia of Rhizoctonia solani byspraying an agar suspension containing the fungi. The inoculatedseedlings were grown in a dark damp place at 28° C. for 4 days, and thecontrolling effect was examined. The results are shown in Table 8.

                  TABLE 8                                                         ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (2)        200             5                                                  (4)        200             5                                                  (5)        200             5                                                  (6)        200             5                                                  (8)        200             5                                                 (14)        200             5                                                 (16)        200             5                                                 (17)        200             5                                                 (18)        200             5                                                 (20)        200             5                                                 (21)        200             5                                                 (22)        200             5                                                 (23)        200             5                                                 (24)        200             5                                                 (26)        200             5                                                 (28)        200             5                                                 (30)        200             5                                                 (31)        200             5                                                 (33)        200             5                                                 (34)        200             5                                                 (35)        200             5                                                 (37)        200             5                                                 (38)        200             5                                                 (40)        200             5                                                 (42)        200             5                                                 (44)        200             5                                                 (47)        200             5                                                 (50)        200             5                                                 (51)        200             5                                                 (52)        200             5                                                 (53)        200             5                                                 (54)        200             5                                                 (59)        200             5                                                 (60)        200             5                                                 (62)        200             5                                                 (63)        200             5                                                 (64)        200             5                                                 (65)        200             5                                                 (75)        200             5                                                 Reference    60             4                                                 compound B                                                                    ______________________________________                                    

TEST EXAMPLE 4

Test for preventive controlling effect on eyespot (Pseudocercosporellaherpotrichoides) of wheat

Wheat seeds (var.: Norin No. 73) were sown in the sandy loam filled in aplastic pot. After raising for 10 days in a greenhouse, the seedlingswere subjected to foliage application with a spray liquid of theemulsion prepared according to Formulation Example 4 which was dilutedwith water to the given concentrations. After application, the seedlingswere air-dried and then inoculated with MBC-resistant spores ofPseudocercosporella herpotrichoides by spraying a suspension containingthe spore. The inoculated seedlings were grown in a dark damp place at15° C. for 4 days, further incubated for 4 days under illumination, andthe controlling effect was examined. The results are shown in Table 9.

                  TABLE 9                                                         ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (1)        500             5                                                  (2)        500             5                                                  (3)        500             5                                                  (4)        500             5                                                  (5)        500             5                                                  (6)        500             5                                                  (7)        500             5                                                  (8)        500             5                                                  (9)        500             5                                                 (10)        500             5                                                 (11)        500             5                                                 (12)        500             5                                                 (13)        500             5                                                 (14)        500             5                                                 (15)        500             5                                                 (16)        500             5                                                 (17)        500             5                                                 (18)        500             5                                                 (19)        500             5                                                 (20)        500             5                                                 (21)        500             5                                                 (22)        500             5                                                 (23)        500             5                                                 (24)        500             5                                                 (25)        500             5                                                 (26)        500             5                                                 (27)        500             5                                                 (28)        500             5                                                 (29)        500             5                                                 (30)        500             5                                                 (31)        500             5                                                 (32)        500             5                                                 (33)        500             5                                                 (34)        500             5                                                 (35)        500             5                                                 (36)        500             5                                                 (37)        500             5                                                 (38)        500             5                                                 (39)        500             5                                                 (40)        500             5                                                 (41)        500             5                                                 (43)        500             5                                                 (44)        500             5                                                 (46)        500             5                                                 (47)        500             5                                                 (48)        500             5                                                 (49)        500             5                                                 (50)        500             5                                                 (51)        500             5                                                 (52)        500             5                                                 (53)        500             5                                                 (54)        500             5                                                 (55)        500             5                                                 (56)        500             5                                                 (57)        500             5                                                 (58)        500             5                                                 (59)        500             5                                                 (60)        500             5                                                 (61)        500             5                                                 (62)        500             5                                                 (63)        500             5                                                 (64)        500             5                                                 (65)        500             5                                                 (66)        500             5                                                 (67)        500             5                                                 (68)        500             5                                                 (70)        500             5                                                 (71)        500             5                                                 (72)        500             5                                                 (73)        500             5                                                 (74)        500             5                                                 (75)        500             5                                                 (76)        500             5                                                 Reference   500             0                                                 compound C                                                                    ______________________________________                                    

TEST EXAMPLE 5

Test for curative controlling effect on speckled leaf blotch (Septoriatritici) of wheat

Wheat seeds (var.: Norin No. 73) were sown in the sandy loam filled in aplastic pot. After raising for 8 days in a greenhouse, the seedlingswere inoculated with spores of Septoria tritici by spraying a suspensionof spores. The inoculated seedlings were grown in a dark damp place at15° C. for 3 days, and then grown for 4 days under lightening. Theseedlings were subjected to foliage application with a spray liquid ofthe wettable powder prepared according to Formulation Example 1 whichwas diluted with water to the given concentration. After application,the seedlings were grown at 15° C. for 11 days under illumination, andthe controlling effect was examined. The results are shown in Table 10.

                  TABLE 10                                                        ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (1)        200             5                                                  (2)        200             5                                                  (3)        200             5                                                  (4)        200             5                                                  (5)        200             5                                                  (6)        200             5                                                  (7)        200             5                                                  (8)        200             5                                                  (9)        200             5                                                 (10)        200             5                                                 (11)        200             5                                                 (13)        200             5                                                 (14)        200             5                                                 (15)        200             5                                                 (16)        200             5                                                 (17)        200             5                                                 (18)        200             5                                                 (19)        200             5                                                 (20)        200             5                                                 (21)        200             5                                                 (22)        200             5                                                 (23)        200             5                                                 (24)        200             5                                                 (25)        200             5                                                 (26)        200             5                                                 (27)        200             5                                                 (28)        200             5                                                 (29)        200             5                                                 (30)        200             5                                                 (31)        200             5                                                 (32)        200             5                                                 (33)        200             5                                                 (34)        200             5                                                 (35)        200             5                                                 (36)        200             5                                                 (37)        200             5                                                 (38)        200             5                                                 (39)        200             5                                                 (40)        200             5                                                 (41)        200             5                                                 (42)        200             5                                                 (43)        200             5                                                 (44)        200             5                                                 (45)        200             5                                                 (46)        200             5                                                 (47)        200             5                                                 (48)        200             5                                                 (49)        200             5                                                 (50)        200             5                                                 (51)        200             5                                                 (52)        200             5                                                 (54)        200             5                                                 (55)        200             5                                                 (56)        200             5                                                 (57)        200             5                                                 (58)        200             5                                                 (59)        200             5                                                 (60)        200             5                                                 (61)        200             5                                                 (62)        200             5                                                 (63)        200             5                                                 (64)        200             5                                                 (65)        200             5                                                 (66)        200             5                                                 (67)        200             5                                                 (68)        200             5                                                 (69)        200             5                                                 (70)        200             5                                                 (71)        200             5                                                 (72)        200             5                                                 (73)        200             5                                                 (74)        200             5                                                 (75)        200             5                                                 (76)        200             5                                                 Reference   500             0                                                 compound E                                                                    ______________________________________                                    

TEST EXAMPLE 6

Test for preventive controlling effect on scab (Venturia inaequalis) ofapple

Apple seeds were sown in the sandy loam filled in a plastic pot. Afterraising for 20 days in a greenhouse, the seedlings, with the fourth tofifth foliage leaves open were subjected to foliage application with aspray liquid of the wettable powder prepared according to FormulationExample 1 which was diluted with water to the given concentrations.After application, the seedlings were air-dried and then inoculated withspores of Venturia inaequalis by spraying a suspension containing thespores. The inoculated seedlings were grown in a dark damp place at 15°C. for 4 days, and then grown under lightening for 15 days. Thecontrolling effect was examined. The results are shown in Table 11.

                  TABLE 11                                                        ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (2)        500             5                                                  (4)        500             5                                                  (5)        500             5                                                  (6)        500             5                                                  (7)        500             5                                                 (11)        500             5                                                 (15)        500             5                                                 (17)        500             5                                                 (20)        500             5                                                 (21)        500             5                                                 (22)        500             5                                                 (24)        500             5                                                 (27)        500             5                                                 (28)        500             5                                                 (29)        500             5                                                 (30)        500             5                                                 (32)        500             5                                                 (33)        500             5                                                 (35)        500             5                                                 (39)        500             5                                                 (40)        500             5                                                 (42)        500             5                                                 (43)        500             5                                                 (44)        500             5                                                 (49)        500             5                                                 (52)        500             5                                                 (57)        500             5                                                 (61)        500             5                                                 (63)        500             5                                                 (68)        500             5                                                 (74)        500             5                                                 (75)        500             5                                                 (76)        500             5                                                 Reference   500             4                                                 compound D                                                                    ______________________________________                                    

TEST EXAMPLE 7

Test for preventive controlling effect on anthracnose (Colletotrichumlagenarium) of cucumber

Cucumber seeds (var.: Sagami hanjiro) were sown in the sandy loam filledin a plastic pot. After raising for 14 days in a greenhouse, theseedlings were subjected to foliage application with a spray liquid ofthe emulsion prepared according to Formulation Example 4 which wasdiluted with water to the given concentrations. After application, theseedlings were air-dried and then inoculated with spores ofColletotrichum lagenarium by spraying a suspension containing thespores. The inoculated seedlings were left to stand in a dark damp placeat 23° C. for one day and then were grown under lightening for 4 days.The controlling effect was examined. The results are shown in Table 12.

                  TABLE 12                                                        ______________________________________                                        Compound     Concentration of                                                                              Control                                          No.          active ingredient (ppm)                                                                       effect                                           ______________________________________                                        Present                                                                       compound                                                                       (2)         500             5                                                 (3)         500             5                                                 (4)         500             5                                                 (5)         500             5                                                 (7)         500             5                                                 (8)         500             5                                                (10)         500             5                                                (11)         500             5                                                (12)         500             5                                                (13)         500             5                                                (15)         500             5                                                (16)         500             5                                                (17)         500             5                                                (18)         500             5                                                (20)         500             5                                                (21)         500             5                                                (22)         500             5                                                (23)         500             5                                                (24)         500             5                                                (25)         500             5                                                (27)         500             5                                                (28)         500             5                                                (29)         500             5                                                (30)         500             5                                                (31)         500             5                                                (32)         500             5                                                (33)         500             5                                                (34)         500             5                                                (35)         500             5                                                (36)         500             5                                                (37)         500             5                                                (39)         500             5                                                (40)         500             5                                                (41)         500             5                                                (43)         500             5                                                (44)         500             5                                                (45)         500             5                                                (46)         500             5                                                (47)         500             5                                                (49)         500             5                                                (50)         500             5                                                (53)         500             5                                                (54)         500             5                                                (55)         500             5                                                (56)         500             5                                                (57)         500             5                                                (59)         500             5                                                (60)         500             5                                                (63)         500             5                                                (64)         500             5                                                (65)         500             5                                                (66)         500             5                                                (68)         500             5                                                (69)         500             5                                                (70)         500             5                                                (71)         500             5                                                (72)         500             5                                                (73)         500             5                                                (74)         500             5                                                (75)         500             5                                                (76)         500             5                                                Reference    500             4                                                compound D                                                                    ______________________________________                                    

TEST EXAMPLE 8

Test for curative controlling effect on powdery mildew (Erysiphegraminis f. sp. tritici) of wheat

Wheat seeds (var.: Norin No. 78) were sown in the sandy loam filled in aplastic pot. After raising for 10 days in a greenhouse, the seedlingswere inoculated with spores of Erysiphe graminis f. sp. tritici. Theinoculated seedlings were grown at 23° C. for 3 days. The seedlings weresubjected to foliage application with a spray liquid of the suspensionprepared according to Formulation Example 2 which was diluted with waterto the given concentrations. After application, the seedlings were grownin a greenhouse at 23° C. for 7 days, and the controlling effect wasexamined. The results are shown in Table 13.

                  TABLE 13                                                        ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (3)        500             5                                                  (4)        500             5                                                  (5)        500             5                                                  (6)        500             5                                                 (14)        500             5                                                 (15)        500             5                                                 (16)        500             5                                                 (17)        500             5                                                 (18)        500             5                                                 (19)        500             5                                                 (20)        500             5                                                 (21)        500             5                                                 (22)        500             5                                                 (23)        500             5                                                 (24)        500             5                                                 (25)        500             5                                                 (27)        500             5                                                 (28)        500             5                                                 (29)        500             5                                                 (31)        500             5                                                 (35)        500             5                                                 (36)        500             5                                                 (37)        500             5                                                 (39)        500             5                                                 (42)        500             5                                                 (44)        500             5                                                 (47)        500             5                                                 (49)        500             5                                                 (51)        500             5                                                 (52)        500             5                                                 (59)        500             5                                                 (60)        500             5                                                 (62)        500             5                                                 (63)        500             5                                                 (64)        500             5                                                 (65)        500             5                                                 (68)        500             5                                                 (70)        500             5                                                 (71)        500             5                                                 ______________________________________                                    

TEST EXAMPLE 9

Test for preventive controlling effect on gray mold (Botrytis cinerea)of cucumber

Cucumber seeds (var.: Sagami hanjiro) were sown in the sandy loam filledin a plastic pot. After raising for 14 days in a greenhouse, theseedlings were subjected to foliage application with a spray liquid ofthe emulsion prepared according to Formulation Example 4 which wasdiluted with water to the given concentrations. After application, theseedlings were air-dried and then inoculated with mycelia of Botrytiscinerea which is resistant to benzimidazole.thiophanate fungicide. Theinoculated seedlings were grown in a dark damp place at 15° C. for 3days, and the controlling effect was examined. The results are shown inTable 14.

                  TABLE 14                                                        ______________________________________                                        Compound     Concentration of                                                                              Control                                          No.          active ingredient (ppm)                                                                       effect                                           ______________________________________                                        Present                                                                       compound                                                                       (1)         500             5                                                 (2)         500             5                                                 (5)         500             5                                                (13)         500             5                                                (15)         500             5                                                (18)         500             5                                                (23)         500             5                                                (24)         500             5                                                (30)         500             5                                                (31)         500             5                                                (33)         500             5                                                (34)         500             5                                                (35)         500             5                                                (37)         500             5                                                (39)         500             5                                                (40)         500             5                                                (44)         500             5                                                (49)         500             5                                                (50)         500             5                                                (51)         500             5                                                (52)         500             5                                                (54)         500             5                                                (56)         500             5                                                (65)         500             5                                                (71)         500             5                                                Reference    500             0                                                compound C                                                                    ______________________________________                                    

TEST EXAMPLE 10

Test for curative controlling effect on leaf rust (Puccinia recondita)of wheat

Wheat seeds (var.: Norin No. 73) were sown in the sandy loam filled in aplastic pot. After raising for 10 days in a greenhouse, the seedlingswere inoculated with spores of Puccinia recondita. The inoculatedseedlings were left to stand in a dark damp place for one day, and thensubjecteed to foliage application with a spray liquid of the emulsionprepared according to Formulation Example 4 which was diluted with waterto the given concentrations. After application, the seedlings were grownunder lightening at 23° C. for 7 days. The controlling effect wasexamined. The test resuts are shown in Table 15.

                  TABLE 15                                                        ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                      (15)        500             5                                                 (17)        500             5                                                 (18)        500             5                                                 (21)        500             5                                                 (23)        500             5                                                 (27)        500             5                                                 (28)        500             5                                                 (31)        500             5                                                 (39)        500             5                                                 (47)        500             5                                                 (60)        500             5                                                 (71)        500             5                                                 ______________________________________                                    

TEST EXAMPLE 11

Test for preventive controlling effect on late blight (Phytophthorainfestans) of tomato

Tomato seeds (var.: Ponterosa) were sown in the sandy loam filled in aplastic pot. After raising for 20 days in a greenhouse, the seedlings,with the second to third foliage leaves open, were subjected to foliageapplication with a spray liquid of the wettable powder preparedaccording to Formulation Example 1 which was diluted with water to thegiven concentrations. After application, the seedlings were air-driedand then inoculated with Phytophthora infestans by spraying a suspensioncontaining the spores. The inoculated seedlings were grown in a dampplace at 20° C. for one day, and then grown in a greenhouse for 5 days,and the controlling effect was examined. The results are shown in Table16.

                  TABLE 16                                                        ______________________________________                                        Compound    Concentration of                                                                              Control                                           No.         active ingredient (ppm)                                                                       effect                                            ______________________________________                                        Present                                                                       compound                                                                       (6)        500             5                                                 (11)        500             5                                                 (15)        500             5                                                 (18)        500             5                                                 (23)        500             5                                                 (27)        500             5                                                 (34)        500             5                                                 (35)        500             5                                                 (43)        500             5                                                 (71)        500             5                                                 (74)        500             5                                                 (75)        500             5                                                 (76)        500             5                                                 ______________________________________                                    

We claim:
 1. A pyridinylpyrimidine derivative of the formula: ##STR166##or a salt thereof, wherein R₁ may be the same or different and is loweralkyl, lower alkoxy, lower haloalkyl or halogen; n is 0, 1, 2, 3, 4 or5; R₂ and R₃, which may be the same or different, each representhydrogen or lower alkyl; R₄ is hydrogen or lower alkyl; R₅ is hydrogen,lower alkyl or halogen, or R₄ and R₅ together represent a polymethylenegroup of the formula: --CH₂)_(m) in which m is 3 or 4; and R₆ ishydrogen, lower alkyl, lower alkoxy or lower alkylthio.
 2. Apyridinylpyrimidine derivative according to claim 1, wherein R₁ may bethe same or different and is C₁ -C₃ alkyl, C₁ -C₃ alkoxy, C₁ -C₃haloalkyl or halogen; n is 0, 1 or 3; R₂ is hydrogen or methyl; R₃ ishydrogen or C₁ -C₄ alkyl; R₄ is hydrogen, methyl or ethyl; R₅ ishydrogen, methyl, ethyl or halogen and R₆ is hydrogen, methyl, ethyl,methoxy, ethoxy or methylthio.
 3. A pyridinylpyrimidine derivativeaccording to claim 1, wherein R₁ may be the same or different and ismethyl, ethyl, methoxy, C₁ or C₂ haloalkyl or halogen, n is 0, 1, 2 or3, R₂ and R₃, which may be the same or different, each representhydrogen or methyl, R₄ is methyl, R₅ is hydrogen or methyl, and R₆ ishydrogen, methyl or methoxy.
 4. A pyridinylpyrimidine derivativeaccording to claim 1, wherein R₁ may be the same or different and ismethyl, trifluoromethyl, fluorine or chlorine, n is 0, 1 or 2, R₂ ishydrogen or methyl, R₃ is hydrogen, R₄ is methyl, R₅ is hydrogen ormethyl and R₆ is hydrogen or methyl. 5.4-Methyl-2-(6-phenyl-2-pyridinyl)pyrimidine or a salt thereof. 6.4-Methyl-2-(5-methyl-6-phenyl-2-pyridinyl)pyrimidine or a salt thereof.7. 4,5-Dimethyl-2-(5-methyl-6-phenyl-2-pyridinyl)pyrimidine or a saltthereof.
 8. 4-Methyl-2-(5-methyl-6-p-tolyl-2-pyridinyl)pyrimidine or asalt thereof.
 9. 2-(6-o-Chlorophenyl-2-pyridinyl)-4-methylpyrimidine ora salt thereof. 10.2-(6-o-Chlorophenyl-5-methyl-2-pyridinyl)-4-methylpyrimidine or a saltthereof. 11.4-Methyl-2-(6-α,α,α-trifluoro-o-tolyl-2-pyridinyl)pyrimidine or a saltthereof.
 12. 4,6-Dimethyl-2-(6-phenyl-2-pyridinyl)pyrimidine or a saltthereof.
 13. 4-Methoxy-6-methyl-2-(6-phenyl-2-pyridinyl)pyrimidine or asalt thereof. 14.2-(6-m-Chlorophenyl-2-pyridinyl)-4-methoxy-6-methylpyrimidine or a saltthereof.
 15. A plant disease protectant which comprises as an activeingredient an effective amount of a pyridinylpyrimidine derivative ofthe formula: ##STR167## or a salt thereof, wherein R₁ may be the same ordifferent and is lower alkyl, lower alkoxy, lower haloalkyl or halogen;n is 0, 1, 2, 3, 4 or 5; R₂ and R₃, which may be the same or different,each represent hydrogen or lower alkyl; R₄ is hydrogen or lower alkyl;R₅ is hydrogen, lower alkyl or halogen, or R₄ and R₅ together representa polymethylene group of the formula: --CH₂)_(m) in which m is 3 or 4;and R₆ is hydrogen, lower alkyl, lower alkoxy or lower alkylthio, and aninert carrier.
 16. A plant disease protectant which comprises as anactive ingredient an effective amount of the pyridinylpyrimidinederivative or a salt thereof as claimed in any one of claims 2 to 14 andan inert carrier.
 17. A method for controlling plant pathogenic fungiwhich comprises applying to plant pathogenic fungi an effective amountof the pyridinylpyrimidine derivative of the formula: ##STR168## or asalt thereof, wherein R₁ may be the same or different and is loweralkyl, lower alkoxy, lower haloalkyl or halogen; n is 0, 1, 2, 3, 4 or5; R₂ and R₃, which may be the same or different, each representhydrogen or lower alkyl; R₄ is hydrogen or lower alkyl; R₅ is hydrogen,lower alkyl or halogen, or R₄ and R₅ together represent a polymethylenegroup of the formula: --CH₂)_(m) in which m is 3 or 4; and R₆ ishydrogen, lower alkyl, lower alkoxy or lower alkylthio.